Ex Parte Nagasawa

Patent Trial and Appeal Board

Jan 30, 2013

12182354 (P.T.A.B. Jan. 30, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/182,354 07/30/2008 Herbert T. Nagasawa 135714.00211 3624
80512 7590 01/30/2013
Pepper Hamilton LLP
400 Berwyn Park
899 Cassatt Road
Berwyn, PA 19312-1183
EXAMINER
PESELEV, ELLI
ART UNIT PAPER NUMBER
1623
MAIL DATE DELIVERY MODE
01/30/2013 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HERBERT T. NAGASAWA
__________

Appeal 2012-000864
Application 12/182,354
Technology Center 1600
__________

Before TONI R. SCHEINER, LORA M. GREEN, and
ERICA A. FRANKLIN, Administrative Patent Judges.

FRANKLIN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of increasing ATP and glutathione in a mammal in need thereof and
a method of treating hypoxia in a mammal in need thereof by increasing
glutathione and ATP. The Patent Examiner rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.

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STATEMENT OF THE CASE
The invention concerns administering RibCys (Ribose-Cysteine) to a
mammal to increase both ATP and glutathione (GSH). (Spec. 4-5.) The
Specification states:
As well as functioning as a prodrug for cysteine, administration
of effective amounts of RibCys can deliver amounts of ribose to
ATP-depleted tissues that stimulate the in vivo synthesis of
ATP and that also can stimulate the synthesis of NADPH
(nicotinamide adenine dinucleotide phosphate, reduced). This
coenzyme supplies the electrons to glutathione reductase, which
in turn recycles oxidized GSH via GSSG to free GSH, which
resumes its protective role as a cofactor for antioxidant
enzymes in the cell.

(Id. at 5, ll. 14-20.)

Claims 23-40 are on appeal. Claims 23, 27, and 30 are representative
and read as follows:
23. A method of increasing ATP and glutathione in a mammal in need
thereof comprising administering an effective amount of RibCys or a
pharmaceutically acceptable salt thereof to said mammal, wherein said
RibCys increases both ATP and glutathione.

27. The method of claim 23, wherein said RibCys is administered in a
unit dosage form comprising 20% (w/w) of RibCys.

30. A method of treating hypoxia in a mammal in need thereof by
increasing glutathione and ATP comprising administering an effective
amount of RibCys or a pharmaceutically acceptable salt thereof to said
mammal, wherein said RibCys increases glutathione and ATP to treat said
hypoxia.

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The Examiner rejected claims 23-40 under 35 U.S.C. § 103(a) as
unpatentable over Roberts,
1
Ozawa,
2
and St. Cyr.
3

OBVIOUSNESS
The Examiner‟s position is that Roberts disclosed that administering
RibCys increases glutathione (GSH) levels, but did not specifically teach
administration of RibCys to mammals in need of both increased levels of
glutathione and ATP, or for the treatment of hypoxia. (Ans. 4.)
Regarding dependent claims 25, 26, 38, and 39, which are directed to
liquid administration of RibCys further comprising an effective amount of
ribose to inhibit premature dissociation of the RibCys, the Examiner found
that Roberts disclosed that increased levels of ribose inhibited dissociation
of RibCys in liquid. (Id. at 4-5.) Regarding dependent claims 27 and 36,
directed to a unit dosage form comprising 20% (w/w) of RibCys, the
Examiner found that this concentration is within the range disclosed by
Roberts. (Id. at 5.) Further, the Examiner found that “[i]t would have been
within routine experimentation by a person of ordinary skill in the art at the
time of the claimed invention to establish the optimal concentration of
RibCys in liquid.” (Id.)
The Examiner found that Ozawa disclosed a correlation between
depressed levels of glutathione and the overproduction of active oxygens in

1
Jeanette C. Roberts and David J. Francetic, Mechanisms of
Chemoprotection by RibCys, a Thiazolidine Prodrug of L-Cysteine, 1 MED.
CHEM. RES., 213-219 (1991).
2
US Patent No. 5,631,234 issued to Takayuki Ozawa et al., May 20, 1997.
3
Patent No. US 6,218,366 B1 issued to John St. Cyr et al., Apr. 17, 2001.

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relation to ischemia, and that these active oxygens are detected in
mitochondria that produce ATP. (Id.)
The Examiner found that St. Cyr disclosed that one condition that
produces hypoxia is acute or chronic ischemia and further disclosed a
method of raising the hypoxic threshold in a mammal by administering
ribose. (Id.)
The Examiner reasoned that
Based on the teachings [of] Roberts et al, Ozawa et al and St.
Cyr et al, a person having ordinary skill in the art at the time of
the claimed invention would have been motivated to administer
RibCys to a mammal in need of increased levels of glutathione
and ATP and to treat hypoxia in a mammal by administration of
RibCys because such a person would have had a reasonable
expectation of success.

(Ans. 5-6.)
Regarding claims 23-29, Appellant asserts that the Examiner has not
established that “the combination of . . . references discloses administering
RibCys to a mammal in need of increasing both ATP and glutathione….”
(App. Br. 20.) According to Appellant, a proper construction of the claims,
which recite a “method of increasing ATP and glutathione in a mammal in
need thereof” (see, e.g., Claim 23) “is that the method be practiced in order
to provide the specific outcome, which in this instance is an increase in ATP
and glutathione” (App. Br. 19)(citing Jansen v. Rexall Sundown, 342 F.3d
1329, 1333-34 (Fed. Cir. 2003)). Appellant asserts that the claimed method
must not be construed “as a statement of effect that may or may not be
desired or appreciated.” (Id. at 20.) Additionally, Appellant asserts that the
Examiner has not shown that one of skill in the art would have had a
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reasonable expectation of successfully increasing ATP and glutathione by
administering RibCys. (Id.) According to Appellant, while St. Cyr
disclosed administering ribose results in an increase of ATP, ribose and
Ribose-Cysteine are different molecules and the Examiner has not shown
that the two are equivalents such that it would have been obvious to simply
substitute one for the other. (Id.)
Regarding claims 30-40, Appellant asserts that the Examiner has not
established that “the combination of the references discloses administering
RibCys to a mammal in need of increasing both ATP and glutathione to treat
hypoxia” (id. at 23) or that “one of skill in the art would have had a
reasonable expectation of success in treating hypoxia by increasing ATP and
glutathione by the administration of RibCys” (id. at 24).
Appellant also asserts that dependent claims 25-27, 36, 38 and 39 are
also not obvious and that in the Final Rejection the Examiner did not
specifically address the limitations in these claims. (Id. at 25.) The
Examiner specifically discussed these rejections in the Answer, as set forth
above. (Ans. 4-5.) In the Reply Brief, Appellant asserts that this discussion
in the Answer constitutes a new ground of rejection. (Reply Br. 4.)
Appellant acknowledges that the reference used in the rejection are the same
as in the Final Rejection, but asserts that Appellant has “not had a „fair
opportunity to react to the thrust of the rejection‟ for all of the claims.”
(Id.)(quoting In re Kronig, 539 F.2d 1300, 1302-03 (CCPA 1976)).
Also in the Reply Brief, Appellant addresses the Examiner‟s rationale
for rejecting these dependent claims. Appellant asserts that the Examiner
has not provided evidence or even an explanation establishing that it would
have been within routine experimentation by a person of ordinary skill in the
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art at the time of the invention to establish the optimal concentration of
RibCys in liquid. (Reply Br. 6.) Further, regarding dependent claims 27 and
36, directed to a unit dosage form comprising 20% (w/w) of RibCys,
Appellant asserts that “no range is disclosed in Roberts.” (Id. at 7.) Rather,
Appellant asserts that Roberts disclosed testing “distinct amounts of RibCys,
such as 1 mg/ml, 10 mg/ml and 100 mg/ml.” (Id.)
Regarding dependent claims 25, 26, 38, and 39, which are directed to
liquid administration of RibCys further comprising an effective amount of
ribose to inhibit premature dissociation of the RibCys, Appellant
acknowledges that Roberts disclosed that “the initial rapid dissociation seen
in Figure 1A was also eliminated with increasing concentration of ribose.”
(Id.)(citing Roberts 215). However, Appellant asserts that Roberts did “not
teach or suggest that this would be effective in the presently claimed method
or that it would only require routine experimentation to inhibit premature
dissociation of RibCys in the context of the presently claimed invention.”
(Id.)
Analysis
I. Independent Claim 23 and Dependent Claims 24, 28, and 29
After considering all the evidence and arguments, we conclude that
the record supports a conclusion of prima facie obviousness for independent
claim 23. In particular, we are not persuaded of nonobviousness by
Appellant‟s assertion that the prior art did not teach or suggest administering
RibCys to a mammal in need of increasing both ATP and GSH. (See App.
Br. 20.) Roberts disclosed a method of administering RibCys to reduce
hepatotoxicity by increasing GSH. (Roberts 214; Ans. 4.) Roberts
explained that RibCys is a prodrug of L-cysteine. (Roberts 214.) As
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described in the Background of the Invention of the instant Specification, the
biosynthesis of GSH involves two sequential reactions that utilize ATP and
that are catalyzed by two enzymes using three precursor amino acids L-
glutamic acid, L-cysteine, and glycine. (Spec. 1, ll. 22-25.) Also as
acknowledged by the Specification:
All substrate-level reactants occur at near enzyme-saturating
concentrations in vivo with the exception of L-cysteine, whose
cellular concentration is exceedingly low. Therefore, the first
reaction in which L-cysteine is required, i.e., the synthesis of γ-
L-glutamyl-L-cysteine, is the rate-limiting step of glutathione
biosynthesis. Thus, the availability of intracellular L-cysteine is
a critical factor in the overall biosynthesis of GSH, [and]
sufficient stores of ATP.

(Id. at ll. 26-31.) Thus, we find that a subject in need of increased GSH,
e.g., to reduce hepatotoxicity as discussed by Roberts, would have
particularly been a subject in need of the factors required for the
biosynthesis of GSH, i.e., L-cysteine and sufficient stores of ATP. Roberts‟
administration of RibCys to such patients inherently provided both of these
factors, although Roberts‟ discussion of the compound was directed
primarily to its function as a prodrug of L-cysteine. See MEHL/Biophile
Int'l Corp. v. Milgraum, 192 F.3d 1362, 1366 (Fed. Cir. 1999) (“Where …
the result is a necessary consequence of what was deliberately intended, it is
of no import that the article's authors did not appreciate the results.”); see
also Perricone v. Medicis Pharmaceutical Corp., 432 F.3d 1368, 1375-76
(Fed. Cir. 2005) and In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990)
(both noting that an appreciation of a new benefit of an old process does not
render that process patentable).
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Accordingly, we affirm the rejection of independent claim 23.
Appellants have not raised separate arguments for the rejection of claims 24,
28, and 29, which depend from claim 23. Accordingly, we also affirm the
rejection of these dependent claims.
II. Dependent claims 25 and 26
In the Reply Brief, Appellant asserts that the Examiner‟s articulation
of the reasons allegedly supporting the rejection of claims 25-27, 36, 38, and
39 for the first time in the Answer constitutes a new ground of rejection that
merits reopening prosecution. (Reply Br. 4-5.) When an Appellant believes
that an Examiner's Answer contains a new ground of rejection not identified
as such, the Appellant may file a petition to the Director under 37 C.F.R. §
1.181(a) within two months of the mailing date of the Examiner's Answer
requesting that a ground of rejection set forth in the Answer be designated a
new ground of rejection or the argument is waived. See MPEP §
1207.03(IV). There is no record of Appellant having filed such a petition in
this matter. Since no new ground of rejection has been designated,
prosecution may not be re-opened. See id.; 37 C.F.R. § 41.39.
Also in the Reply Brief, Appellant asserts that dependent claims 25
and 26 would not have been obvious to a skilled artisan at the time of the
invention. Claims 25 and 26 require the administration of RibCys to further
comprise an effective amount of ribose to inhibit premature dissociation of
the RibCys. (App. Br. 28, Claims App‟x.) As Appellant acknowledges,
Roberts disclosed that increased levels of ribose inhibited dissociation of
RibCys in liquid. (See Reply Br. 7; Ans. 4-5.) Thus, we agree with the
Examiner that a person of ordinary skill in the art would have found it
obvious to administer an effective amount of ribose to inhibit premature
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dissociation of the liquid RibCys administered in the method of Roberts
based upon this disclosure in Roberts. Appellant has not persuasively
established otherwise my merely asserting that Roberts did “not teach or
suggest that this would be effective in the presently claimed method or that it
would only require routine experimentation to inhibit premature dissociation
of RibCys in the context of the presently claimed invention.” (Reply Br. 7.)
Accordingly, we affirm the rejection of dependent claims 25 and 26.
III. Dependent claim 27
Dependent claim 27 is directed to a unit dosage form comprising 20%
(w/w) of RibCys. (App. Br. 28, Claims App‟x.) We agree with Appellant
that Roberts‟ disclosure of testing “distinct amounts of RibCys, such as 1
mg/ml, 10 mg/ml and 100 mg/ml” did not teach or suggest a range of unit
dosage forms, i.e., a range between 1 and 100mg/ml, such that the claimed
20% (w/w) would have been obvious. (Reply Br. 7.) Moreover, we do not
find that the Examiner established that a skilled artisan would have achieved
this claimed unit dosage form with routine experimentation. (See Ans. 5.)
Accordingly, we reverse the rejection of dependent claim 27.
IV. Independent Claim 30 and Dependent Claims 31-40
After considering all the evidence and arguments, we agree with
Appellant that the record does not support a conclusion of prima facie
obviousness for independent claim 30, which is directed to administering
RibCys to treat hypoxia. (See App. Br. 28, Claims App‟x.) The Examiner
found that Roberts did not disclose administering RibCys to treat hypoxia.
(Ans. 4.) The Examiner found that Ozawa disclosed a correlation between
depressed levels of glutathione and the overproduction of active oxygens in
relation to ischemia, and that these active oxygens are detected in
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mitochondria that produce ATP. (Id. at 5.) Additionally, the Examiner
found that St. Cyr disclosed that acute or chronic ischemia produces hypoxia
and further disclosed a method of raising the hypoxic threshold in a mammal
by administering ribose. (Id.) However, what is missing from the rejection
is some articulated reasoning with some rational underpinnings to support
the Examiner‟s conclusory statement that:
Based on the teachings [of] Roberts et al, Ozawa et al and St.
Cyr et al, a person having ordinary skill in the art at the time of
the claimed invention would have been motivated to administer
RibCys to a mammal in need of increased levels of glutathione
and ATP and to treat hypoxia in a mammal by administration of
RibCys because such a person would have had a reasonable
expectation of success.

(Ans. 5-6.) See In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006); KSR Int’l
Co. v. Teleflex Inc., 550 U.S. 398, 417-18 (2007). In other words, the
Examiner has not explained what would have led one of ordinary skill in the
art to combine the relevant teachings of the cited prior art to arrive at the
claimed invention of treating hypoxia with RibCys. See In re Fine, 837 F.2d
1071, 1074 (Fed. Cir. 1988).
Accordingly, we reverse the rejection of independent claim 30 and its
dependent claims 31-40.

SUMMARY
We affirm the rejection of claims 23-26, 28, and 29;
we reverse the rejection of claims 27 and 30-40.

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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED-IN-PART

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